Molecular Bloodhounds

Antibodies, the body’s own biosensors, recognize and bind to foreign molecules with astonishing precision. Antibodies are incorporated in many medical diagnostic tests, but researchers have long hoped for ways to make cheap and long-lasting artificial antibodies-synthetic molecules which, when added to a patient’s blood sample, would detect and latch onto specific disease markers just as effectively as natural antibodies. New work on polymer structures that mimic the binding action of natural antibodies may be bringing scientists a step closer to that goal.

To build the artificial antibodies, chemists at the University of Illinois at Urbana-Champaign start with a template molecule similar in shape to the one they ultimately want to detect. To that, they attach a handful of dendrimers, highly branched polymer molecules. After chemically linking the tips of the dendrimers to create a rigid shell around the entire structure, the researchers remove the template molecule from the center by adding water, which breaks the template’s temporary bonds with the dendrimers. The end result: a dendrimer shell bearing in its center a single imprint to which molecules can bind.

Such artificial antibodies can be fabricated with the same sensitivity as natural antibodies, and they can be tailored to bind to any number of molecules, even acting as detectors of chemical and biowarfare agents in the air, says chemist Steven Zimmerman, the project’s lead investigator. Best of all, Zimmerman says, “The technique is really cheap, and the biosensors are reusable. You just wash them off.”

“I think this is an elegant demonstration of the [polymer imprinting] technique,” says James Baker, director of the Center for Biologic Nanotechnology at the University of Michigan. The real test of the technique’s potential, however, will be “whether or not these dendrimers can detect a single protein in a blood sample containing perhaps 10,000 different proteins,” says Baker. At that level of sensitivity, dendrimer-based artificial antibodies might find commercial applications in AIDS or hepatitis blood tests that currently use natural antibodies. Beyond diagnostic tests, says Zimmerman, could be coatings made of dye-containing dendrimers that change color in the presence of nerve toxins and other agents. And that could mean bright prospects for artificial antibodies.